Stress granule formation as a marker of cellular toxicity in lung organoids

Cells regulate protein synthesis under stressful circumstances by forming cytoplasmic RNA granules, termed stress granules (SGs). SGs are membrane-less organelles that function as a protective mechanism in response to stress. They function through liquid-liquid phase separation, which is a vital process comprising 2 distinct de-mixed liquid phases. The components of SGs, such as G3BP1, can serve as biomarkers of cell toxicity. Respiratory diseases are among the leading causes of death globally. After the humidifier disinfectant disaster in Korea in 2011, social concerns over respiratory disease-related deaths have been raised, and the importance of inhalation toxicity testing has been emphasized. Traditionally, in vivo animal models have been used to assess inhalation toxicity, but these models still have limitations owing to physiological differences between species. To overcome these limitations, human immortalized lung epithelial and lung cancer cell lines have been used to evaluate lung toxicity in vitro. Human stem cell-derived 3-dimensional organoid technology has recently been developed in various research fields, including lung toxicity. This review discusses SG-related proteins as potential biomarkers for lung toxicity assessment, especially in human lung organoids under stress conditions, such as exposure to toxic chemicals.